title: A 4-selenocysteine, 2-selenocysteine insertion sequence (SECIS) element methionine sulfoxide reductase from Metridium senile reveals a non-catalytic function of selenocysteines.
abstract: Selenocysteine (Sec) residues occur in thiol oxidoreductase families, and functionally characterized selenoenzymes typically have a single Sec residue used directly for redox catalysis. However, how new Sec residues evolve and whether non-catalytic Sec residues exist in proteins is not known. Here, we computationally identified several genes with multiple Sec insertion sequence (SECIS) elements, one of which was a methionine-R-sulfoxide reductase (MsrB) homolog from Metridium senile that has four in-frame UGA codons and two nearly identical SECIS elements. One of the UGA codons corresponded to the conserved catalytic Sec or Cys in MsrBs, whereas the three other UGA codons evolved recently and had no homologs with Sec or Cys in these positions. Metabolic (75)Se labeling showed that all four in-frame UGA codons supported Sec insertion and that both SECIS elements were functional and collaborated in Sec insertion at each UGA codon. Interestingly, recombinant M. senile MsrB bound iron, and further analyses suggested the possibility of binding an iron-sulfur cluster by the protein. These data show that Sec residues may appear transiently in genes containing SECIS elements and be adapted for non-catalytic functions.
authors.affiliation: Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: Byung Cheon
authors.initials: BC
authors.lastname: Lee
authors.forename: Alexey V
authors.initials: AV
authors.lastname: Lobanov
authors.forename: Stefano M
authors.initials: SM
authors.lastname: Marino
authors.forename: Alaattin
authors.initials: A
authors.lastname: Kaya
authors.forename: Javier
authors.initials: J
authors.lastname: Seravalli
authors.forename: Dolph L
authors.initials: DL
authors.lastname: Hatfield
authors.forename: Vadim N
authors.initials: VN
authors.lastname: Gladyshev
mesh_terms: D000818:Animals; D002384:Catalysis; D003062:Codon; D007501:Iron / Q000378:metabolism; D051150:Methionine Sulfoxide Reductases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012615:Sea Anemones / Q000201:enzymology*; D017279:Selenocysteine / Q000235:genetics / Q000378:metabolism*
chemical_list: D003062:Codon; D011994:Recombinant Proteins; D017279:Selenocysteine; D007501:Iron; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase